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dc.contributor.authorCater, Heather L
dc.contributor.authorGitterman, Daniel
dc.contributor.authorDavis, Susan M
dc.contributor.authorBenham, Christopher D
dc.contributor.authorMorrison, Barclay
dc.contributor.authorSundstrom, Lars E
dc.date.accessioned2012-08-16T11:01:16Z
dc.date.available2012-08-16T11:01:16Z
dc.date.issued2007
dc.identifier.citationCater , H L , Gitterman , D , Davis , S M , Benham , C D , Morrison , B & Sundstrom , L E 2007 , ' Stretch-induced injury in organotypic hippocampal slice cultures reproduces in vivo post-traumatic neurodegeneration : role of glutamate receptors and voltage-dependent calcium channels ' , Journal of Neurochemistry , vol. 101 , no. 2 , pp. 434-47 . https://doi.org/10.1111/j.1471-4159.2006.04379.x
dc.identifier.issn0022-3042
dc.identifier.otherPURE: 560701
dc.identifier.otherPURE UUID: 16ad8066-22c6-4bb4-a5c8-49721f1649cf
dc.identifier.otherPubMed: 17250683
dc.identifier.otherScopus: 34047112884
dc.identifier.urihttp://hdl.handle.net/2299/8872
dc.description.abstractThe relationship between an initial mechanical event causing brain tissue deformation and delayed neurodegeneration in vivo is complex because of the multiplicity of factors involved. We have used a simplified brain surrogate based on rat hippocampal slices grown on deformable silicone membranes to study stretch-induced traumatic brain injury. Traumatic injury was induced by stretching the culture substrate, and the biological response characterized after 4 days. Morphological abnormalities consistent with traumatic injury in humans were widely observed in injured cultures. Synaptic function was significantly reduced after a severe injury. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 attenuated neuronal damage, prevented loss of microtubule-associated protein 2 immunoreactivity and attenuated reduction of synaptic function. In contrast, the NMDA receptor antagonists 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and GYKI53655, were neuroprotective in a moderate but not a severe injury paradigm. Nifedipine, an L-type voltage-dependent calcium channel antagonist was protective only after a moderate injury, whereas omega-conotoxin attenuated damage following severe injury. These results indicate that the mechanism of damage following stretch injury is complex and varies depending on the severity of the insult. In conclusion, the pharmacological, morphological and electrophysiological responses of organotypic hippocampal slice cultures to stretch injury were similar to those observed in vivo. Our model provides an alternative to animal testing for understanding the mechanisms of post-traumatic delayed cell death and could be used as a high-content screen to discover neuroprotective compounds before advancing to in vivo models.en
dc.format.extent14
dc.language.isoeng
dc.relation.ispartofJournal of Neurochemistry
dc.subjectAnimals
dc.subjectBrain Injuries
dc.subjectCalcium Channel Blockers
dc.subjectCalcium Channels
dc.subjectExcitatory Amino Acid Antagonists
dc.subjectExcitatory Postsynaptic Potentials
dc.subjectGlutamic Acid
dc.subjectHippocampus
dc.subjectMembranes, Artificial
dc.subjectMicrotubule-Associated Proteins
dc.subjectModels, Neurological
dc.subjectNerve Degeneration
dc.subjectNeuroprotective Agents
dc.subjectNeurotoxins
dc.subjectOrgan Culture Techniques
dc.subjectPhysical Stimulation
dc.subjectRats
dc.subjectReceptors, Glutamate
dc.subjectSilicones
dc.subjectStress, Mechanical
dc.subjectSynaptic Transmission
dc.titleStretch-induced injury in organotypic hippocampal slice cultures reproduces in vivo post-traumatic neurodegeneration : role of glutamate receptors and voltage-dependent calcium channelsen
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.description.statusPeer reviewed
dcterms.dateAccepted2007
rioxxterms.versionofrecordhttps://doi.org/10.1111/j.1471-4159.2006.04379.x
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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